Sedation is an important component of care for pediatric patients in the intensive care unit (ICU) not only for their physiologic well being, but also for patient safety and the safety of the caregivers.
Benzodiazepines and opioids, such as fentanyl or morphine, are frequently administered to provide sedation and analgesia in the pediatric intensive care unit (PICU). Propofol has been shown to cause severe, life-threatening metabolic alterations in children including circulatory failure, and is not indicated in the pediatric population for continuous intensive care sedation. (See Propofol Injectable Emulsion [package insert]. Lake Forest Ill.: Hospira, Inc.: 2008). With prolonged administration of benzodiazepines and opioids, tolerance and physical dependence may develop. Midazolam sedation in some pediatric patients causes oversedation alternating with under sedation and paradoxical agitation. (See Midazolam hydrochloride [Package Insert]. Lake Forest, Ill.: Hospira, Inc.: 2005).
Recent reports of apoptosis and neurodevelopment abnormalities in neonatal and infant animal models from gamma-amino butyric acid (GABA)-agonist drugs have heightened the concern of sedating neonates and infants with benzodiazepines. (See Young et al. Brit J Pharma 2005; 146:189-197; and Sander et al. Brit J Anaesth 2008; 101 (5): 597-609). The concomitant administration of opioids further complicates pediatric patient management because of respiratory depression. Therefore, there is a significant unmet need for safe and effective sedation and analgesia in pediatric patients.
Dexmedetomidine (Precedex®) is a highly selective alpha-2 adrenergic agonist with significant sedative, analgesic, and anxiolytic effects. Dexmedetomidine is currently approved by the FDA for sedation of initially intubated and mechanically ventilated adult patients in an intensive care setting, and is also approved for sedation of non-intubated adult patients as a component of monitored anesthesia care during surgical or diagnostic procedures. Dexmedetomidine is the only sedative approved in the United Sates for administration as a continuous infusion in non-intubated ICU patients because it does not significantly affect respiratory drive.
Sedation with dexmedetomidine for adult patients in the ICU has been widely studied. When used in combination with opioids or benzodiazepines, dexmedetomidine often allows for a reduction in the doses of the other agents, reducing the risk of respiratory depression.